Numerical solutions of the compressible 3-D boundary-layer equations for aerospace configurations with emphasis on LFC

The application of stability theory in Laminar Flow Control (LFC) research requires that density and velocity profiles be specified throughout the viscous flow field of interest. These profile values must be as numerically accurate as possible and free of any numerically induced oscillations. Guidelines for the present research project are presented: develop an efficient and accurate procedure for solving the 3-D boundary layer equation for aerospace configurations; develop an interface program to couple selected 3-D inviscid programs that span the subsonic to hypersonic Mach number range; and document and release software to the LFC community. The interface program was found to be a dependable approach for developing a user friendly procedure for generating the boundary-layer grid and transforming an inviscid solution from a relatively coarse grid to a sufficiently fine boundary-layer grid. The boundary-layer program was shown to be fourth-order accurate in the direction normal to the wall boundary and second-order accurate in planes parallel to the boundary. The fourth-order accuracy allows accurate calculations with as few as one-fifth the number of grid points required for conventional second-order schemes

Polarisation rotation of slow light with orbital angular momentum in ultracold atomic gases

We consider the propagation of slow light with an orbital angular momentum (OAM) in a moving atomic medium. We have derived a general equation of motion and applied it in analysing propagation of slow light with an OAM in a rotating medium, such as a vortex lattice. We have shown that the OAM of slow light manifests itself in a rotation of the polarisation plane of linearly polarised light. To extract a pure rotational phase shift, we suggest to measure a difference in the angle of the polarisation plane rotation by two consecutive light beams with opposite OAM. The differential angle $\Delta\alpha_{\ell}$ is proportional to the rotation frequency of the medium $\omega_{\mathrm{rot}}$ and the winding number $\ell$ of light, and is inversely proportional to the group velocity of light. For slow light the angle $\Delta\alpha_{\ell}$ should be large enough to be detectable. The effect can be used as a tool for measuring the rotation frequency $\omega_{\mathrm{rot}}$ of the medium.Comment: 5 pages, 1 figur

Exploiting similarity in turbulent shear flows for turbulence modeling

It is well known that current k-epsilon models cannot predict the flow over a flat plate and its wake. In an effort to address this issue and other issues associated with turbulence closure, a new approach for turbulence modeling is proposed which exploits similarities in the flow field. Thus, if we consider the flow over a flat plate and its wake, then in addition to taking advantage of the log-law region, we can exploit the fact that the flow becomes self-similar in the far wake. This latter behavior makes it possible to cast the governing equations as a set of total differential equations. Solutions of this set and comparison with measured shear stress and velocity profiles yields the desired set of model constants. Such a set is, in general, different from other sets of model constants. The rational for such an approach is that if we can correctly model the flow over a flat plate and its far wake, then we can have a better chance of predicting the behavior in between. It is to be noted that the approach does not appeal, in any way, to the decay of homogeneous turbulence. This is because the asymptotic behavior of the flow under consideration is not representative of the decay of homogeneous turbulence

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC

This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.Peer reviewe

Personality traits and behavioral patterns associated with systolic blood pressure levels in college males

1. 1. Seventy-four young white male college students (out of an original pool of 800 examined) were selected for having high or low systolic readings taken on a registration line. These students were then classified according to their paired casual, usual, and sustained levels of systolic blood pressure. Of 21 persons with a high paired casual systolic blood pressure (two independent determinations in excess of 140 mm Hg), 16 were also characterized as belonging to a `usual high' group (blood pressure in excess of 131 mm on resting and repeated home readings). A `sustained' high blood pressure group (n = 11) was further obtained by selecting those who were `high' on their paired casual and their `usual' blood pressure levels. These blood pressure patterns were then related with self ratings on the Cattell 16 PF questionnaire.2. 2. A consistent elevation to the upper range of normal in the systolic blood pressure of these college males was associated with `submissiveness' and `sensitivity' as defined by Cattell's 16 PF questionnaire. Subjects with `high paired casual' systolic blood pressures described themselves as motivated to obtain social contacts, but in a `sensitive' and `anxious' manner.3. 3. Subjects who were later selected for having a single high systolic blood pressure reading taken on first entering the physician's office (their second casual reading) tended more frequently to yield in an argument and then afterwards to change their private opinions toward agreement with partners who had an initially low systolic reading.4. 4. Whereas obesity was highly correlated with higher systolic levels, the psychological correlates of obesity were different from those related to elevated `casual' or `sustained' blood pressure. Obese subjects in this population appeared to be physically active, and more confident, though somewhat anxious under the stress of school examinations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32127/1/0000180.pd

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Immunological correlates of mycobacterial growth inhibition describe a spectrum of tuberculosis infection

A major contribution to the burden of Tuberculosis (TB) comes from latent Mycobacterium tuberculosis infections (LTBI) becoming clinically active. TB and LTBI probably exist as a spectrum and currently there are no correlates available to identify individuals with LTBI most at risk of developing active disease. We set out to identify immune parameters associated with ex vivo mycobacterial growth control among individuals with active TB disease or LTBI to define the spectrum of TB infection. We used a whole blood mycobacterial growth inhibition assay to generate a functional profile of growth control among individuals with TB, LTBI or uninfected controls. We subsequently used a multi-platform approach to identify an immune signature associated with this profile. We show, for the first time, that patients with active disease had the greatest control of mycobacterial growth, whilst there was a continuum of responses among latently infected patients, likely related to the degree of immune activation in response to bacillary load. Control correlated with multiple factors including inflammatory monocytes, activated and atypical memory B cells, IgG1 responses to TB-specific antigens and serum cytokines/chemokines. Our findings offer a method to stratify subclinical TB infections and the future potential to identify individuals most at risk of progressing to active disease and benefit from chemoprophylaxis.</p